Molecularly imprinted polymers (MIPs) are functional materials capable of molecular recognition and other biorelevant functions and can be prepared with ease in a tailor-made fashion by copolymerization in the presence of a crosslinker and a template molecule (the target molecule or its analog) conjugated with a functional monomer(s). These robust and affordable synthetic polymer receptors are highly accepted as favorable alternatives to biomacromolecules such as antibodies and enzymes. This article provides a critical review of the present state of MIPs to establish perspectives on this technique via a survey of early to contemporary work, mainly conducted by the authors, covering new principles and methodology to generate MIPs. These include the design and synthesis of new functional monomers and crosslinkers to develop and/or introduce new functionalities, new polymerization methods to improve the imprint effect, and highly sensitive MIP-based assays and sensors.